P909: RENAL RESPONSE OF POMALIDOMIDE WITH BORTEZOMIB AND DEXAMETHASONE IN NEWLY DIAGNOSED MULTIPLE MYELOMA PATIENTS WITH RENAL IMPAIRMENT
Authors: Y. Jian, L. Chang, M. Shi, Y. Sun, X. Chu, H. Xue, X. Shen, J. Ma, G. Jia, Y. Feng, Z. Xi, Y. Zhao, Y. Ma, J. Xiao, G. Ma, Q. Wang, W. Huang, L. Bao, Y. Dong, H. Zhou, C. Sun, G. Su, Y. Yan, Q. Saiyin, L. Su, S. Gao, W. Tian, X. Sun, H. Jing, D. Gao, W. Chen, J. Li, W. Gao
Journal: HemaSphere (2022)

Background: Renal impairment (RI) is a common complication of multiple myeloma (MM), usually related to poor outcomes. Bortezomib-based regimens have been recommended as first-line therapy of MM with RI. Recently, pomalidomide also has shown significant efficacy and an acceptable safety profile in MM patients with RI. However, few prospective studies evaluated the value of combination of pomalidomide with bortezomib and dexamethasone (PVD) in these special patients. Aims: To evaluate the renal response, hematological response and safety of pomalidomide in combination with bortezomib and dexamethasone (PVD) as first-line therapy in newly diagnosed MM (NDMM) with RI. Methods: This study is an ongoing, prospective, open-label, multicenter, phase 2 study (ChiCTR2100043748). Eligible adult NDMM patients with MM-related RI (defined as estimated glomerular filtration rate (eGFR) < 40ml/min) who had measurable disease are enrolled in the study. Exclusion criteria included RI caused by other reasons than tubular nephropathy, such as renal amyloidosis, light chain deposition disease, etc. Patients received a maximum of 9 cycles of PVD therapy. For transplant-eligible patients, autologous stem cell transplantation (ASCT) was administrated after 3 to 6 PVD cycles. Primary endpoint was renal overall response rate (ORR) at 3 months. Secondary endpoints included best renal response, hematological response, minimal residual disease (MRD), progression-free survival (PFS), overall survival (OS) and safety. Both hematological response and renal response were assessed by International Myeloma Working Group (IMWG) criteria. Results: Between Feb 28, 2021 and Jan 21, 2022, sixty-one patients were enrolled across 28 Chinese hospitals, with a median age of 61 years (range: 38-79); 60.7% were male. Fifty-eight (95.1%) patients had cytogenetic information by FISH at diagnosis, fourteen (24.1%) of them had high-risk cytogenetic abnormalities (defined as t(4;14), t(14;16), and/or del(17p)). Median serum creatine level and eGFR were 349 μmol/L (range: 155-1718) and 12.9 mL/min (range: 2.5-36.3), respectively. Twelve (19.7%) patients received dialysis. Median number of PVD treatment cycles was 4 (range: 1-9). Six patients had received ASCT. Among 56 patients with evaluable hematological response, ORR was 91.1% (69.6% ≥VGPR, 41.1% CR). Forty-eight (78.7%) patients had got the primary endpoint with renal ORR at 3 months, which was 89.4% (48.9% ≥ renal-PR, 35.4% renal-CR). Median time to best renal response was 1.5 months (range: 0.3-11.0). Dialysis independence rate was 58.3% (7/12). Median time from first dose of PVD therapy to dialysis independence was 1 month (range: 0.5-2.0). Rapid reduction of serum free light chain (FLC) was seen at the first cycle of PVD therapy. Median reduction proportion of involved FLC at C1D8 was 77.5% (range: 0-98.5%), while at C1D22 was 91.7% (range: 0-99.9%). The most common adverse effects (incidence >10%) were infection (29.5%), myelosuppression (18.0%), peripheral neuritis (16.4%) and skin rash (11.5%). Median follow-up time was 6 months. Twelve patients (19.7%) discontinued PVD treatment, mainly due to toxicity and patients’ intention. Median PFS and OS has not been reached. Summary/Conclusion: PVD regimen is an effective and well-tolerated regimen for NDMM patients with RI, which offered high renal response (renal ORR at 3 months of 89.4%).